The US Food and Drug Administration sent Warning Letters to Bayer HealthCare concerning two unlawful, over-the-counter (OTC) Aspirin products - Bayer Women's Low Dose Aspirin + Calcium (Bayer Women's) and Bayer Aspirin with Heart Advantage (Bayer Heart Advantage).

The products, which contain aspirin with either phytosterols or calcium, are unapproved new drugs that require an approved new drug application in order to be legally marketed. In addition to being labelled for use as a pain reliever, both products are labelled for use in reducing the risks of heart disease. Bayer Women's is also labelled for use in 'fighting' osteoporosis. Neither product has been approved by the FDA for such uses. These drug uses require a health care professional's diagnosis and supervision, and therefore these products cannot be labelled for use by consumers and sold over-the-counter (OTC).

"The FDA considers these products new drugs and thus they must undergo the FDA's drug approval process," said Mike Chappell, the FDA's acting associate commissioner for regulatory affairs. "The FDA will take enforcement action against manufacturers found to be violating the law or attempting to circumvent the drug approval process."

Bayer Heart Advantage combines aspirin and phytosterols in a single tablet. Bayer Women's combines aspirin and calcium carbonate in a single tablet. The products are labelled as being a combination of a drug and a dietary supplement, but when a drug and a dietary supplement are combined in a single tablet, the product is regulated by FDA as a drug.

According to the labelling, the phytosterols in Bayer Heart Advantage are intended to lower blood cholesterol and the calcium in Bayer Women's is intended to strengthen bones to fight osteoporosis. Although certain calcium-containing dietary supplements may bear claims to reduce the risk of osteoporosis, products that are labelled to 'fight' or otherwise treat osteoporosis are drugs that require FDA approval. Similarly, although certain phytosterol-containing dietary supplements may bear claims to reduce the risk of coronary heart disease, and may note that the mechanism by which phytosterols achieve this effect is through lowering blood cholesterol, direct claims to lower cholesterol are claims to prevent or treat coronary heart disease and hypercholesterolemia, which is also a disease. Products bearing such claims require an approved new drug application from FDA in order to be legally marketed, and cannot be legally marketed for OTC use.

Under its OTC drug monograph system, FDA allows some drugs to be marketed without first obtaining agency approval. These drugs must comply with applicable monographs, that is, regulations that set requirements for the drugs' labelling and formulation, as well as the indications (uses) for which the drugs can be marketed. OTC drugs that do not meet these requirements and that lack FDA approval are considered illegal, unapproved drugs. Bayer Heart Advantage and Bayer Women's do not meet the conditions in any applicable OTC monograph, and do not have FDA approval. Therefore, Bayer Heart Advantage and Bayer Women's are unapproved new drugs.

In addition, Bayer Heart Advantage and Bayer Women's are misbranded because their labelling lacks adequate directions for use by consumers. In order for a drug to have adequate directions for use, the directions must be written so that consumers can use the product safely for its intended purpose, without the supervision of a health care professional. The use of these products for treatment of heart disease and osteoporosis requires diagnosis and supervision by a health care professional to ensure safe use. Therefore, it is not possible, in OTC drug product labelling, for these products to have adequate directions for their intended uses.

The products also are misbranded because their labelling do not have adequate warnings and are misleading. Among other things, the labelling for the aspirin in the products includes directions and warnings regarding short term use, but these directions and warnings are contradicted by other directions for the phytosterols and calcium that promote the products' daily use without any time limits. The result is a mixed message about the products' purposes and the length of time for which the products can be safely used.

"The marketing of these unapproved drugs is troubling," said Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research. "Because OTC drugs are widely used by consumers, without supervision by a doctor or other health care professional, the overuse or misuse of these aspirin-containing products can put consumers at risk for internal bleeding and other adverse events. It is essential that companies obtain FDA approval and fully comply with FDA regulations."

Although the FDA is not aware of significant adverse events associated with these products, the agency is concerned because neither product has been approved by FDA for its marketed uses.

These actions reaffirm the position taken by FDA in two previously issued Warning Letters - one sent to BF Ascher & Co, Inc, Lenexa, KS, regarding Melagesic PM, and the other to Omni Nutraceuticals, Inc, Los Angeles, CA regarding Inholtra Joint Pain products. In those letters, the FDA stated that drug ingredients combined with dietary ingredients in a single dosage form require agency approval to be legally marketed in the United States.

Companies that do not resolve violations in FDA Warning Letters risk enforcement action, such as injunctions and/or seizure of illegal products.